[Neutrophil-lymphocyte ratio as predictor of mortality in patients with necrotizing fasciitis]. / Índice neutrófilo-linfocito como predictor de mortalidad en pacientes con fascitis necrotizante.

Background: Necrotizing fasciitis (NF) can affect any soft tissue and skin of the body. Its progression is rapid and it is associated with a high mortality rate. Therefore, the search for easily accessible and low-cost biomarkers that could predict the prognosis of patients with NF is necessary. Objective: To evaluate the role of neutrophil-lymphocyte ratio (NLR) as a predictor of mortality in patients with NF. Material and methods: Observational, cross-sectional, retrospective and analytical study of patients admitted between April and October 2020 in a tertiary-care hospital. The statistical tests used for the comparison of variables between the study groups were chi-square, Fisher's exact, Student's t and Mann-Whitney U. A receiver operating characteristic (ROC) curve was performed to determine the accuracy of NLR in predicting mortality in patients with NF. Results: A total of 25 patients were included and stratified into non-survivors and survivors. The non-survivor group had an elevated NLR value compared to survivors (15.57 [13.75] vs. 7.91 [4.13]; p = 0.065). The NLR had an area under the curve (AUC) of 0.729 (95% confidence interval [95% CI] 0.516-0.886; p = 0.044), sensitivity of 77.78% (40-97.2), and specificity of 75% (47.6-92.7). The optimal cut-off point obtained for NLR was > 9.21. Conclusions: An NLR value > 9.21 could be a predictor of mortality in patients with NF.

Introducción: la fascitis necrotizante (FN) puede afectar cualquier tejido blando y piel del cuerpo. Su progresión es rápida y está relacionada con un índice de mortalidad alto. Por lo tanto, la búsqueda de biomarcadores de fácil acceso y bajo costo que puedan predecir el pronóstico de los pacientes con FN es necesaria. Objetivo: evaluar el papel del índice neutrofilo-linfocito (INL) como un predictor de mortalidad en los pacientes con FN. Material y métodos: estudio observacional, transversal, retrospectivo y analítico de pacientes admitidos entre abril y octubre del 2020 en un hospital de tercer nivel. Las pruebas estadísticas utilizadas para la comparación de las variables entre los grupos de estudio fueron chi cuadrado, exacta de Fisher, t de Student y U de Mann-Whitney. Una curva característica operativa del receptor (ROC) fue realizada para determinar la precisión del INL en la predicción de mortalidad en pacientes con FN. Resultados: un total de 25 pacientes fueron incluidos y estratificados en no sobrevivientes y sobrevivientes. El grupo no sobreviviente tuvo un valor elevado del INL en comparación con los sobrevivientes (15.57 [13.75] frente a 7.91 [4.13]; p = 0.065). El INL tuvo un área bajo la curva (AUC) de 0.729 (intervalo de confianza del 95% [IC 95%] 0.516-0.886; p = 0.044), sensibilidad de 77.78% (40-97.2) y especificidad de 75% (47.6-92.7). El punto de corte óptimo obtenido para el INL fue > 9.21. Conclusiones: un valor de INL > 9.21 podría ser un predictor de mortalidad en los pacientes con FN.

International normalised ratio as an independent predictor of mortality in limb necrotising fasciitis with sepsis.

INTRODUCTION: Necrotising fasciitis with sepsis is a life threatening disease. The aim of this study was to analyse the association between international normalised ratio (INR) and mortality in sepsis patients with necrotising fasciitis. METHODS: A retrospective review was undertaken of 106 patients suffering from necrotising fasciitis with sepsis between November 2007 and December 2016. Data on comorbidities, clinical manifestations, laboratory findings, causative microbiological organisms, APACHE II (Acute Physiology and Chronic Health Evaluation II) score and outcomes were extracted. Logistic regression was carried out to examine the factors affecting mortality. RESULTS: Forty patients (37.7%) died. There was no significant difference in the white blood count (WBC) for the survivor and non-survivor groups. Non-survivors had a lower mean oxygenation index (OI) (288.7mmHg vs 329.4mmHg, p=0.032) and platelet count (PC) (139.5 vs 214.8 x 109/l, p=0.028), and a higher mean INR (1.9 vs 1.3, p=0.000), activated partial thromboplastin time (APTT) (54.6 vs 44.2 seconds, p=0.005) and serum creatinine (2.3mg/dl vs 1.4mg/dl, p=0.007). Mortality in patients with INR >1.5 was significantly higher than in those with INR <1.5 when all risk factors (WBC, PC, OI, INR, APTT, creatinine) were considered (odds ratio: 4.414, 95% confidence interval: 1.263-15.428, p=0.020). Even after adjusting for age, sex, bacteraemia, diabetes and hepatic disorders, the data still exhibited elevated mortality for patients with INR >1.5 (odds ratio: 5.600, 95% confidence interval: 1.415-22.166, p=0.014). CONCLUSIONS: INR is a significant independent predictor of mortality in sepsis patients diagnosed with necrotising fasciitis.

Evaluation of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score for detecting necrotizing soft tissue infections in patients with diabetes and lower extremity infection.

AIMS: The aim of this pilot study was to assess the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), a scoring system for Necrotizing Soft Tissue Infections, to diagnose Necrotizing Soft Tissue Infections of the lower extremity in patients with diabetes. METHODS: Sixty-nine patients with lower extremity infections were prospectively enrolled. The Laboratory Risk Indicator for Necrotizing Fasciitis was calculated and logistic regression was performed for each laboratory value. RESULTS: The Laboratory Risk Indicator for Necrotizing Fasciitis was associated with Necrotizing Soft Tissue Infection diagnosis in patients with diabetes (p = 0.01). Sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 69%, 16.6%, and 100% respectively. Elevated C-reactive protein (OR 1.01, p = 0.02, 95% CI [1.002-1.23]) and white blood cell count (OR 1.34, p < 0.01, 95% CI [1.1-1.7]) were associated with Necrotizing Soft Tissue Infection. CONCLUSIONS: The Laboratory Risk Indicator for Necrotizing Fasciitis was useful as a negative predictor of Necrotizing Soft Tissue Infection while C- reactive protein and white blood cell count may have value as individual predictors. We recommend high clinical suspicion of Necrotizing Soft Tissue Infections in diabetics as laboratory evaluation may be non-specific.

Influence of hyperbaric oxygen therapy on thrombus formation ability in humans.

Background: Hyperbaric oxygen (HBO2) therapy was introduced nearly 300 years ago. However, its effect on thrombus formation is unclear. This may be because platelet and coagulation functions are unstable, yielding variable results; hence, accurate measurement is difficult. Our study aimed to analyze changes in thrombus formation before and after HBO2 therapy by using a total thrombus formation analysis system (TTAS). Methods: Six patients were prescribed HBO2 therapy for skin and soft tissue ulcers, and necrotic fasciitis. Blood samples were collected immediately before and after treatment. Then samples were put into a reservoir that connected to AR-chip to assess changes in the thrombus formation ability of both platelets and coagulation factors. We examined the differences in the thrombus formation ability using T-TAS. Time until the onset of white thrombus formation (T10) and complete occlusion of the capillary (T80) were analyzed by a two-way repeated measure analysis of variance (ANOVA). Results: The duration to pressure increase of samples after HBO2 therapy was longer than the duration before HBO2 therapy (p<0.05). This suggests decreased clot adhesiveness to the inner surface of the simulated blood vessel and reduced clot formation ability. Conclusions: The results for T10 and T80 suggest that HBO2 therapy reduced thrombus formation ability in the enrolled patients. We believe that T-TAS is a promising method to predict the efficacy of HBO2 therapy.

Necrotizing Fasciitis Within 72 hours After Presentation with Skin and Skin Structure Infection.

INTRODUCTION: A small percentage of patients with skin infections later develop necrotizing fasciitis (NF). Diagnostic testing is needed to identify patients with skin infections at low risk of NF who could be discharged from the emergency department (ED) after antibiotic initiation. Elevated lactate has been associated with NF; existing estimates of the frequency of NF are based on retrospective reviews, and cases often lack testing for lactate. We present the incidence of patients with skin infections who developed NF and their baseline lactates. METHODS: In four phase-3 trials, 2883 adults with complicated or acute bacterial skin and skin structure infections were randomized to dalbavancin or comparator, with early and late follow-up visits through Day 28. We prospectively collected baseline plasma lactates in one trial to assess an association with NF. RESULTS: NF was diagnosed in 3/2883 patients (0.1%); all three survived. In the study with prospectively collected baseline lactates (n = 622), 15/622 (2.4%) had a lactate ≥4 millimoles per liter (mmol/L), including 3/622 (0.5%) with a lactate ≥7 mmol/L. NF was not seen in patients with a lactate <4 mmol/L; NF was seen in 1/15 (6.7%) with a lactate ≥4 mmol/L, including 1/3 (33.3%) with lactate ≥7 mmol/L. CONCLUSIONS: NF incidence within 72 hours of antibiotic initiation in patients with complicated or acute bacterial skin and skin structure infections was extremely low (0.1%) and occurred in 6.7% with a lactate ≥4 mmol/L. Lactate <4 mmol/L can be used to identify patients at low risk of NF who could be safely discharged from the ED after antibiotic initiation.

Complement Activation Is Associated With Mortality in Patients With Necrotizing Soft-Tissue Infections-A Prospective Observational Study.

Aim: We assessed whether different complement factors and complement activation products were associated with poor outcome in patients with necrotizing soft-tissue infection (NSTI). Methods: We conducted a prospective, observational study in an intensive care unit where treatment of NSTI is centralized at a national level. In 135 NSTI patients and 65 control patients, admission levels of MASP-1, MASP-2, MASP-3, C4, C3, complement activation products C4c, C3bc, and terminal complement complex (TCC) were assessed. Results: The 90-day mortality was 23%. In a Cox regression model adjusted for sex, and SAPS II, a higher than median MASP-1 (HR 0.378, CI 95% [0.164-0.872], p = 0.0226) and C4 (HR 0.162, 95% CI [0.060-0.438], p = 0.0003), C4c/C4 ratio (HR 2.290 95% CI [1.078-4.867], p = 0.0312), C3bc (HR 2.664 95% CI [1.195-5.938], p = 0.0166), and C3bc/C3 ratio (HR 4.041 95% CI [1.673-9.758], p = 0.0019) were associated with 90-day mortality, while MASP-2, C4c, C3, and TCC were not. C4 had the highest ROC-AUC (0.748, [95% CI 0.649-0.847]), which was comparable to the AUC for SOFA score (0.753, [95% CI 0.649-0.857]), and SAPS II (0.862 [95% CI 0.795-0.929]). Conclusion: In adjusted analyses, high admission levels of the C4c/C4 ratio, C3bc, and the C3bc/C3 ratio were significantly associated with a higher risk of death after 90 days while high admission levels of MASP-1 and C4 were associated with lower risk. In this cohort, these variables are better predictors of mortality in NSTI than C-reactive protein and Procalcitonin. C4's ability to predict mortality was comparable to the well-established scoring systems SAPS score II and SOFA on day 1.

Prospective Validation of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score for Necrotizing Fasciitis of the Extremities.

OBJECTIVES: The Laboratory Risk Indicator for Necrotizing Fasciitis score was developed as a clinical decision tool for distinguishing necrotizing fasciitis from other soft tissue infections. We prospectively evaluated the performance of the Laboratory Risk Indicator for Necrotizing Fasciitis score for the diagnosis of patients with necrotizing fasciitis in the extremities. METHODS: We conducted a prospective and observational cohort study of emergency department patients with necrotizing fasciitis or severe cellulitis in the extremities between April 2015 and December 2016. The Laboratory Risk Indicator for Necrotizing Fasciitis score was calculated for every enrolled patient. The sensitivity, specificity, positive predictive value, and negative predictive value of cut-off scores of 6 and 8 were evaluated. The accuracy of the Laboratory Risk Indicator for Necrotizing Fasciitis score was expressed as the area under the receiver operating characteristic curve. RESULTS: A total of 106 patients with necrotizing fasciitis and 825 patients with cellulitis were included. With an Laboratory Risk Indicator for Necrotizing Fasciitis cut-off score ≥6, the sensitivity was 43% (95% confidence interval 34% to 53%), specificity was 83% (95% confidence interval 80% to 86%), positive predictive value was 25% (95% confidence interval 20% to 30%), and negative predictive value was 92% (95% confidence interval 91% to 93%); with an Laboratory Risk Indicator for Necrotizing Fasciitis cut-off score ≥8, the sensitivity was 27% (95% confidence interval 19% to 37%), specificity was 93% (95% confidence interval 91% to 94%), positive predictive value was 33% (95% confidence interval 25% to 42%), and negative predictive value was 91% (95% confidence interval 90% to 92%). The area under the receiver operating characteristic curve for accuracy of the Laboratory Risk Indicator for Necrotizing Fasciitis score was 0.696 (95% CI 0.640 to 0.751). CONCLUSION: The Laboratory Risk Indicator for Necrotizing Fasciitis score may not be an accurate tool for necrotizing fasciitis risk stratification and differentiation between severe cellulitis and necrotizing fasciitis in the emergency department setting based on our study.

Accurate and quick predictor of necrotizing soft tissue infection: Usefulness of the LRINEC score and NSTI assessment score.

OBJECTIVE: The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is a diagnostic tool for necrotizing soft tissue infection (NSTI), which is validated and is considered to have high diagnostic value. However, some experts criticize LRINEC score for consisting of laboratory test results only. METHODS: In this single-center retrospective study, we created a new scoring system (NSTI assessment score; NAS), which also incorporated vital signs as another diagnostic tool for NSTI using cases from our hospital and also evaluated diagnostic accuracy of LRINEC score. We identified NSTI predictors by comparing 24 NSTI patients and 80 non NSTI patients using uni- and multivariate logistic regression analysis, and created NAS based on odds ratio of variables which are statistically significant in the multivariate model. RESULTS: We identified mean arterial pressure, C-reactive protein, hemoglobin, serum creatinine, and glucose as a predictor for NSTI. The maximum value of NAS was 11 points with the cut-off value of 6. Sensitivity, specificity, positive predictive value, and negative predictive value of the NAS for diagnosis of NSTI were 87.5%, 91.3%, 75.0%, and 96.1%, respectively. Area under the receiver operating characteristic curve was 0.926 (0.851-1.00) for the NAS and 0.903 (0.833-0.973) for the LRINEC score, and they were not statistically different (p = 0.167). CONCLUSION: The NAS has high diagnostic accuracy in predicting NSTI, and is comparable with the LRINEC score. The NAS needs to be validated in other cohorts in the future.

Necrotizing Soft Tissue Infections: A Focused Review of Pathophysiology, Diagnosis, Operative Management, Antimicrobial Therapy, and Pediatrics.

Background: Necrotizing fasciitis is a major health problem throughout the world. The purpose of this review is to assist providers with the care of these patients through a better understanding of the pathophysiology and management options. Methods: This is a collaborative review of the literature between members of the Surgical Infection Society of North America and World Society of Emergency Surgery. Results: Necrotizing fasciitis continues to be difficult to manage with the mainstay being early diagnosis and surgical intervention. Recognition of at-risk populations assists with the initiation of treatment, thereby impacting outcomes. Conclusions: Although there are some additional treatment strategies available, surgical debridement and antimicrobial therapy are central to the successful eradication of the disease process.

Air entrapment resembling necrotising fasciitis as a frequent incident following total hip arthroplasty.

In combination with pain and elevated inflammatory parameters that are frequently observed following elective total hip arthroplasty (THA), air entrapment on radiographic images could be indicative of necrotising fasciitis. The aim of the present study was to analyse presence/extent of air entrapment following THA, and to correlate radiological with clinical findings. One-hundred patients undergoing short-stem elective THA (ANA NOVA Alpha Proxy-system) were prospectively included. Patients received pre- and postoperative x-rays (day 1 + discharge) of the affected hip, together with a CT-scan of the lower extremity (discharge). C-reactive-protein-(CRP), leukocyte, haemoglobin-, creatinine-, glucose-, sodium-levels - and based on these the LRINEC score- as well as pain-scores (numeral-rating-scale, NRS) at postoperative days 1, 3 and 5 were documented. Air entrapment was visible in 98% of x-rays taken postoperatively and in 93% of CT-scans at discharge. Leukocyte-levels significantly decreased from postoperative day 1 to 5. CRP-levels had a peak at the 3rd postoperative day (p < 0.001). On discharge-x-rays of patients with low body-mass-indexes, air entrapment was significantly more often visible (p = 0.040). Neither implant-related nor laboratory parameters, LRINEC- or NRS-scores significantly correlated with presence/extent of air entrapment (p > 0.05). Considering the high rate of air entrapment following elective THA postoperatively and at discharge, suspicion of an infection with gas-producing bacteria may only be raised in case of persistent inflammatory parameters, deteriorating general condition and signs of local infection.

An elevated glycemic gap predicts adverse outcomes in diabetic patients with necrotizing fasciitis.

BACKGROUND: Diabetes is the most common comorbidity of necrotizing fasciitis (NF), but the effect of stress-induced hyperglycemia (SIH) on diabetic patients with NF has never been investigated. The aim of this study was to assess whether SIH, as determined by the glycemic gap between admission glucose levels and A1C-derived average glucose levels, predicts adverse outcomes in diabetic patients hospitalized with NF. METHODS: We retrospectively reviewed the glycemic gap and clinical outcomes in 252 diabetic patients hospitalized due to NF from 2011 to 2018 in a single medical center in Taiwan. A receiver operating characteristic (ROC) curve was used to analyze the optimal cutoff values for predicting adverse outcomes. Univariate and multivariate logistic regression analyses were employed to identify significant predictors of adverse outcomes. RESULTS: In total, 194 diabetic NF patients were enrolled. Compared with patients without adverse outcomes, patients with adverse outcomes had significantly higher glycemic gaps, Acute Physiology and Chronic Health Evaluation (APACHE) II scores and C-reactive protein (CRP) levels; lower albumin and hemoglobin levels; greater incidence of limb loss; and longer hospital and intensive care unit stays. The glycemic gap positively correlates with the laboratory risk indicator for NF scores, APACHE II scores and CRP levels. A glycemic gap of 146 mg/dL was the optimal cutoff value for predicting adverse outcomes using the ROC curve. Compared with patients with glycemic gaps ≤146 mg/dL, those with glycemic gaps >146 mg/dL had higher APACHE II scores and incidence rates of adverse outcomes, especially bacteremia and acute kidney injury. Multivariate analysis revealed that a glycemic gap >146 mg/dL and APACHE II score >15 were independent predictors of adverse outcomes, while the presence of hyperglycemia at admission was not. CONCLUSIONS: An elevated glycemic gap was significantly independently associated with adverse outcomes in diabetic NF patients. Further prospective studies are warranted to validate the role of the glycemic gap in NF patients with diabetes.

Usefulness of a risk scale based on procalcitonin for early discrimination between necrotising fasciitis and cellulitis of the extremities. / Utilidad de una escala de riesgo basada en la procalcitonina sérica para la discriminación temprana entre fascitis necrosante y celulitis de las extremidades.

BACKGROUND AND OBJECTIVE: To assess the usefulness of a risk scale based on serum procalcitonin (PCT) compared to the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) scale in the early discrimination between necrotising fasciitis (NF) and cellulitis of the extremities. MATERIALS AND METHODS: Retrospective study of consecutive patients with confirmed diagnosis of NF in one limb (n=11). This study group was compared with 23 consecutive patients with a diagnosis of severe limbs cellulitis during the same period. The clinical data and laboratory parameters were analysed, the main variable was the serum level of PCT upon admission. The capacity for NF diagnosis of the two methods, PCT level and LRINEC scale score, were evaluated by ROC curve and determined by the calculation of the area under the curve (AUC). RESULTS: The AUC was significantly higher with PCT measurement, both as a continuous variable and when the risk was categorised. The cut-off point for the PCT level with the highest AUC under the curve was from 0.87ng/ml (sensitivity 90.9%, specificity 82.6%), whereas it was a score of 5 on the LRINEC scale (sensitivity 72.7%, specificity 82.6%). CONCLUSION: PCT measurement was a more effective method than the LRINEC score for early discrimination between NF and cellulitis of the extremities. A low level of PCT, associated with the patient's clinical status and physical examination is especially useful to rule out an early diagnosis of NF.

Lactate on emergency department arrival as a predictor of in-hospital mortality in necrotizing fasciitis: a retrospective study.

BACKGROUND: Hyperlactatemia is known to be associated with adverse outcome in critical illness. In this study, we attempted to identify if hyperlactatemia on emergency department (ED) arrival is a reliable predictor for in-hospital mortality in necrotizing fasciitis (NF) patients. METHOD: A prospective cohort study of hospitalized patients with NF was conducted in two tertiary teaching hospitals in Taiwan between March 2010 and March 2018. Blood samples were collected in the ED upon arrival, and the lactate levels were determined. Sequential organ failure assessment (SOFA) scores were calculated during the first 24 h after admission. All collected data were statistically analyzed. RESULT: Of the 707 NF patients, 40 (5.66%) died in the hospital. The median (interquartile range) blood lactate level in all NF patients was 3.6 mmol/l (2.2-4.8). The blood lactate level upon ED arrival was significantly associated with mortality (odds ratio [OR] = 1.35; 95% confidence interval [CI], 1.30-1.46; P < 0.001), even after adjustment for age and SOFA score (OR = 1.27; P < 0.001). Multivariate regression analysis showed that a high blood lactate level (OR = 1.17; 95% CI, 1.07-1.29; P = 0.001) and a high SOFA score (OR = 1.15; 95% CI, 1.11-1.20; P < 0.001) were independent risk factors for in-hospital mortality in NF. Blood lactate achieved an area under-the-receiver-operating-characteristic curve (AUC) of 0.79 (P < 0.001) for predicting mortality that was similar to that of SOFA score (AUC = 0.82; P < 0.001). Blood lactate displayed a sensitivity of 62% and a specificity of 86% in predicting mortality at the optimal cutoff value of 5.80 mmol/l. CONCLUSION: In necrotizing fasciitis patients, hyperlactatemia on ED arrival is independently associated with in-hospital mortality. NF patients with hyperlactatemia on ED arrival should be closely monitored for signs of deterioration and consider early and aggressive intervention to prevent mortality.

Biomarkers of Necrotising Soft Tissue Infections Aspects of the Innate Immune Response.

Necrotising soft tissue infection (NSTI) is a life-threatening and rapidly progressing bacterial infection involving one or more layers of the soft tissue compartments causing necrosis. The amputation and mortality rates remain high despite increased focus on the patients. Timely treatment, including surgical intervention, reduces the risk of severe disability and death. However, the lack of pathognomonic signs impedes early diagnosis and treatment. Moreover, the rarity of the disease makes it difficult to conduct large prospective studies, thus prospective research is almost non-existent in this group of patients. Instead data regarding biomarkers are extrapolated from the wide and heterogenic group of patients with sepsis, even though the immunological responses are likely to differ because of the large amount of necrotic tissue seen in patients with NSTI.   We performed the largest prospective, observational studies to date of patients with NSTI in Scandinavia sampled over more than two years with up to a 2.7-year follow-up. Blood samples were taken on admission (baseline) and the following three days and subsequently analysed for relevant plasma biomarkers. We elaborated on three aspects of the innate immune response, which included the investigation of acute-phase proteins, pattern recognition molecules of the lectin complement pathway, and inflammatory cytokines. The objective was to investigate aspects of the innate immune response in patients with NSTI, focusing on biomarkers as prognostic markers of disease severity and mortality. The overall hypothesis was that plasma biomarkers, representing the early innate immune response, can be used as prognostic markers of disease severity and mortality assessed by ICU scoring systems (SAPS II and SOFA score), the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score, presence of septic shock, microbial aetiology, renal replacement therapy, and amputation.   In Study 1, we assessed the following acute-phase proteins in 135 patients with NSTI: pentraxin-3 (PTX3), procalcitonin, and C-reactive protein. We found that a high baseline PTX3 level above the median was significantly associated with the presence of septic shock, amputation, and 180-day mortality, albeit PTX3 was not an independent predictor of mortality. PTX3 and procalcitonin performed equally well, whereas C-reactive protein correlated poorly with clinically relevant outcomes.      In Study 2, we assessed the following plasma pattern recognition molecules in the same cohort as in Study 1: mannose-binding lectin, Ficolin-1, Ficolin-2, and Ficolin-3. We found that baseline Ficolin-2 level below the median was associated with short- and long-term mortality and correlated with the SAPS II, whereas low levels of mannose-binding lectin and Ficolin-3 were associated only with short-term mortality.   In Study 3, we assessed the following inflammatory cytokines in 159 patients with NSTI: interleukin-1ß, interleukin-6, interleukin-10, and tumor necrosis factor-α. We found no significant association between the LRINEC score and baseline cytokine levels. In addition, interleukin-6 had the strongest correlation with the disease severity scores (SAPS II and SOFA score), whereas interleukin-1ß and interleukin-10 had the strongest association with 30-day mortality. Moreover, patients with ß-haemolytic streptococcal infection had higher levels of interleukin-6 and tumor necrosis factor-α compared with each subgroup stratified by microbial aetiology.    This thesis provides new knowledge on the aspects of the innate immune response in patients with NSTI. The results prove that NSTI is characterised by a pronounced inflammatory response and that the innate immune response differs according to disease severity, microbial aetiology, and mortality. Through the three studies we have identified relevant biomarkers that are useful in the risk stratification of patients with NSTI, thus perhaps enhancing prognostication and decision making in these critically ill patients.

Evaluating the Laboratory Risk Indicator to Differentiate Cellulitis from Necrotizing Fasciitis in the Emergency Department.

INTRODUCTION: Necrotizing fasciitis (NF) is an uncommon but rapidly progressive infection that results in gross morbidity and mortality if not treated in its early stages. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is used to distinguish NF from other soft tissue infections such as cellulitis or abscess. This study analyzed the ability of the LRINEC score to accurately rule out NF in patients who were confirmed to have cellulitis, as well as the capability to differentiate cellulitis from NF. METHODS: This was a 10-year retrospective chart-review study that included emergency department (ED) patients ≥18 years old with a diagnosis of cellulitis or NF. We calculated a LRINEC score ranging from 0-13 for each patient with all pertinent laboratory values. Three categories were developed per the original LRINEC score guidelines denoting NF risk stratification: high risk (LRINEC score ≥8), moderate risk (LRINEC score 6-7), and low risk (LRINEC score ≤5). All cases missing laboratory values were due to the absence of a C-reactive protein (CRP) value. Since the score for a negative or positive CRP value for the LRINEC score was 0 or 4 respectively, a LRINEC score of 0 or 1 without a CRP value would have placed the patient in the "low risk" group and a LRINEC score of 8 or greater without CRP value would have placed the patient in the "high risk" group. These patients missing CRP values were added to these respective groups. RESULTS: Among the 948 ED patients with cellulitis, more than one-tenth (10.7%, n=102 of 948) were moderate or high risk for NF based on LRINEC score. Of the 135 ED patients with a diagnosis of NF, 22 patients had valid CRP laboratory values and LRINEC scores were calculated. Among the other 113 patients without CRP values, six patients had a LRINEC score ≥ 8, and 19 patients had a LRINEC score ≤ 1. Thus, a total of 47 patients were further classified based on LRINEC score without a CRP value. More than half of the NF group (63.8%, n=30 of 47) had a low risk based on LRINEC ≤5. Moreover, LRINEC appeared to perform better in the diabetes population than in the non-diabetes population. CONCLUSION: The LRINEC score may not be an accurate tool for NF risk stratification and differentiation between cellulitis and NF in the ED setting. This decision instrument demonstrated a high false positive rate when determining NF risk stratification in confirmed cases of cellulitis and a high false negative rate in cases of confirmed NF.

Laboratory risk indicator for necrotising fasciitis (LRINEC) score for the assessment of early necrotising fasciitis: a systematic review of the literature.

Introduction Early operative debridement of necrotising fasciitis is a major outcome determinant. Identification and diagnosis of such patients can be clinically difficult. The Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score first published in 2004 is based on routinely performed parameters and offers a method for identifying early cases. No literature review has yet been performed on the application of such a score. Methods A systematic review of English-language literature was performed from 2004 to 2014 to identify articles reporting use of LRINEC score and the incidence of necrotising fasciitis. We performed a critical review of PubMed, Medline and Embase in line with the PRISMA statement. A meta-analysis was performed with a random effects model and 95% confidence interval. Suitable correlation coefficient and receiver operating characteristic (ROC) curves were also calculated. Results After application of inclusion criteria, 16 studies with 846 patients were included. The mean LRINEC score in patients with necrotising fasciitis was 6.06. Two papers reported LRINEC score in patients without necrotising fasciitis with a mean 2.45. All six studies with a reported coefficient of variance were < 1; Pearson correlation coefficient was r = 0.637 (P = 0.011). An ROC curve showed an area under the curve of 0.927. Conclusions The LRINEC score is a useful clinical determinant in the diagnosis and surgical treatment of patients with necrotising fasciitis, with a statistically positive correlation between LRINEC score and a true diagnosis of necrotising fasciitis.

Association between cytokine response, the LRINEC score and outcome in patients with necrotising soft tissue infection: a multicentre, prospective study.

Early assessment of necrotising soft tissue infection (NSTI) is challenging. Analysis of inflammatory markers could provide important information about disease severity and guide decision making. For this purpose, we investigated the association between cytokine levels and the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC)-score, disease severity and mortality in NSTI patients. In 159 patients, plasma was analysed for IL-1ß, IL-6, IL-10 and TNF-α upon admission. The severity of NSTI was assessed by SAPS, SOFA score, septic shock, microbial aetiology, renal replacement therapy and amputation. We found no significant difference in cytokine levels according to a LRINEC- score above or below 6 (IL-1ß: 3.0 vs. 1.3; IL-6: 607 vs. 289; IL-10: 38.4 vs. 38.8; TNF-α: 15.1 vs. 7.8 pg/mL, P > 0.05). Patients with ß-haemolytic streptococcal infection had higher level of particularly IL-6. There was no difference in mortality between patients with a LRINEC-score above or below 6. In the adjusted analysis assessing 30-day mortality, the association was strongest for IL-1ß (OR 3.86 [95% CI, 1.43-10.40], P = 0.008) and IL-10 (4.80 [1.67-13.78], P = 0.004). In conclusion, we found no significant association between the LRINEC-score and cytokine levels on admission. IL-6 was consistently associated with disease severity, whereas IL-1ß had the strongest association with 30-day mortality.